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The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism
Open accessAbstract
The endocannabinoid system, with its receptors and ligands, is present in the gut epithelium and enteroendocrine cells, and is able to modulate brain functions, both indirectly through circulating gut-derived factors and directly through the vagus nerve, finally acting on the brain's mechanisms regarding metabolism and behavior. The gut endocannabinoid system also regulates gut motility, permeability, and inflammatory responses. Furthermore, microbiota composition has been shown to influence the activity of the endocannabinoid system. This review examines the interaction between microbiota, intestinal endocannabinoid system, metabolism, and stress responses. We hypothesize that the crosstalk between microbiota and intestinal endocannabinoid system has a prominent role in stress-induced changes in the gut-brain axis affecting metabolic and mental health. Inter-individual differences are commonly observed in stress responses, but mechanisms underlying resilience and vulnerability to stress are far from understood. Both gut microbiota and the endocannabinoid system have been implicated in stress resilience. We also discuss interventions targeting the microbiota and the endocannabinoid system to mitigate metabolic and stress-related disorders.
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“The ECS and GM interact to regulate intestinal homeostasis resulting in relevant functional effects in the gut and CNS (238, 246, 248, 250).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [246]
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“In response to stress, eCB signaling modulates glucocorticoid and CRH signaling in the brain and is crucial in recovering homeostasis (241, 246, 247).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [246]
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Metadata
- Authors
- Srivastava, R. K., Lutz, B., & Ruiz de Azua, I.
- Affiliations
- Indira Gandhi National Tribal University (IN)
- Leibniz Institute for Resilience Research (DE)
- Corresponding author
- Srivastava, Raj Kamal
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2022-05-11
- Volume
- 16
- Pages
- 867267-867267
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC9130962
- OpenAlex
- W4280612876
- Cited by
- 56
- References
- 300
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 16 · 2023: 11
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Gutenberg Open Science (submittedVersion, cc-by-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Gutenberg Open Science (cc-by)
- Funders
- Department of Biotechnology, Ministry of Science and Technology, India
- Science and Engineering Research Board
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, stress response, metabolism, gut-brain axis, vagus nerve, enteroendocrine cells, intestinal motility, intestinal permeability, intestinal inflammation, stress resilience, individual differences, microbiota-targeted interventions, mental health
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